Breakthrough Treatment for Large B-Cell Lymphoma
A cell-based gene therapy, Yescarta (axicabtagene ciloleucel), was approved by the Food and Drug Administration in October 2017 to treat adults with certain kinds of large B-cell lymphoma who have not responded to other kinds of treatment. It is the first gene therapy approved for certain types of non-Hodgkin lymphoma, a cancer of the blood that starts in white blood cells, called lymphocytes (part of the body’s immune system). The FDA approved a similar therapy for pediatric patients last summer. The new therapy is part of an emerging new treatment known as immunotherapy.
Emerging Treatment. Immunotherapy uses the power of the patient’s own immune system to help fight cancer. For years, only surgery, chemotherapy, and radiation therapy were available to treat cancer patients. Immunotherapy has transformed the therapy landscape.
CAR T Cell Therapy. An immunotherapy approach called adoptive cell transfer (ACT) collects and uses patients’ own immune cells to treat their cancers. CAR T cell therapy is one of these and has been found to produce remarkable results. So far, the ACT approach is effective against liquid, or blood tumors, rather than solid tumors, as are found in breast and colorectal cancers, for example. Multiple myeloma also has been targeted for CAR T cell therapy.
Foundation of CAR T Cells. T-cells are considered the workhorses of the immune system, according to the National Cancer Institute, because they play a vital role in galvanizing the immune system to kill pathogen-infected cells.
How It Works. The new therapy involves taking blood from patients and separating out the T-cells; the T cells then are genetically engineered to produce receptors on their surface called chimeric antigen receptors (CARs).
The receptors enable the T cells to recognize and attach to a specific protein, or antigen, on tumor cells. Once the T cells have been engineered to express the antigen-specific CAR, they are cultured in the laboratory and millions more cells are created.
The patient then undergoes chemotherapy treatment, after which the CAR T cells are infused into the patient. There, the engineered ells continue to multiply, and recognize and kill cancer cells that carry the antigen on their surfaces. Laboratories can now create CAR T cells in less than seven days.
Results in lymphoma treatment have been called “incredibly successful,” according to James Kochenderfer, MD, of the National Cancer Institute’s Experimental Transplantation and Immunology Branch.
Side Effects. T cells can release cytokines, chemical “messengers” that help to direct the immune response. But if there is a swift and very large release of cytokines into the bloodstream, high fevers and steep drops in blood pressure can ensue. Patients with the most extensive disease are more prone to more severe cytokine release syndrome (CRS). Tocilizumab (Actemra) has been used to fight the inflammation, and has become a standard therapy for managing severe CRS.
A die-off of B cells is another potential side effect; to compensate, many patients receive immunoglobulin therapy, which provides antibodies to help them fight off infection. Another side effect, swelling in the brain, also has been noted, but appears to be limited.
Solid Tumors. Research on CAR T cells is also being conducted in patients with solid tumors. There currently are more than 180 clinical trials, a large increase over the number four or five years ago.
The breakthroughs in adoptive cell transfer to date are stunning; stand by for more advances in the field of immunotherapy.
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